34 results on '"Williams IP"'
Search Results
2. A study of Hilda asteroids .2. Compositional implications from optical spectroscopy
- Author
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Dahlgren, M, Lagerkvist, CI, Fitzsimmons, A, Williams, IP, Gordon, M, Dahlgren, M, Lagerkvist, CI, Fitzsimmons, A, Williams, IP, and Gordon, M
- Abstract
We obtained 49 reflectance spectra of 23 Hilda asteroids in the wavelength ranges 3850-7650 and 3850-10150 Angstrom during two observing runs in 1992. The primitive D-types dominate and comprise 34% of the numbered Hilda asteroids, while 28% and 2% are P, Addresses: Dahlgren M, ASTRON OBSERV, BOX 515, S-75120 UPPSALA, SWEDEN. QUEENS UNIV BELFAST, DEPT PURE & APPL PHYS, APS DIV, BELFAST BT7 1NN, ANTRIM, NORTH IRELAND. UNIV LONDON QUEEN MARY & WESTFIELD COLL, SCH MATH SCI, ASTRON UNIT, LONDON E1 4NS, ENGLAND
- Published
- 1997
3. Physical studies of asteroids .31. Asteroid photometric observations with the Carlsberg Automatic Meridian Circle
- Author
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Piironen, J, Magnusson, P, Lagerkvist, CI, Williams, IP, Buontempo, ME, Morrison, LV, Piironen, J, Magnusson, P, Lagerkvist, CI, Williams, IP, Buontempo, ME, and Morrison, LV
- Abstract
Photometric observations of 74 asteroids obtained with the Carlsberg Automatic Meridian Circle between January 1990 and December 1993 are presented. The data from individual asteroid apparitions have been fitted by phase curves based on the standard HG ma, Addresses: Piironen J, ASTRON OBSERV, BOX 515, S-75120 UPPSALA, SWEDEN. ASTRON OBSERV, FIN-00014 HELSINKI, FINLAND. UNIV LONDON QUEEN MARY & WESTFIELD COLL, LONDON E1 4NS, ENGLAND. ROYAL GREENWICH OBSERV, CAMBRIDGE CB3 0EZ, ENGLAND. DLR, INST PLANETARY EX
- Published
- 1997
4. Pneumonitis complicating methotrexate therapy for pustular psoriasis
- Author
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Ameen, M, primary, Taylor, DA, additional, Williams, IP, additional, Wells, AU, additional, and Barker, JNWN, additional
- Published
- 2001
- Full Text
- View/download PDF
5. New method for measuring compliance with long term oxygen treatment
- Author
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Harrison Nk, Williams Ip, F. J. C. Millard, A. R. C. Cummin, Shenoy Vs, Newey, Phillips Gd, Ritchie D, and Ward J
- Subjects
Artificial ventilation ,medicine.medical_specialty ,medicine.medical_treatment ,Oxygen concentrator ,chemistry.chemical_element ,Common method ,Oxygen ,medicine ,Humans ,Electrodes ,Monitoring, Physiologic ,General Environmental Science ,business.industry ,Oxygen Inhalation Therapy ,General Engineering ,Reproducibility of Results ,General Medicine ,medicine.disease ,Home Care Services ,Long-Term Care ,Obstructive lung disease ,Term (time) ,Surgery ,Compliance (physiology) ,chemistry ,Emergency medicine ,Patient Compliance ,General Earth and Planetary Sciences ,Delivery system ,Respiratory Insufficiency ,business ,Research Article - Abstract
Long term oxygen treatment used for at least 15 hours a day improves survival in patients with chronic obstructive lung disease and respiratory failure.1,2 In 1989 prescriptions for oxygen for use at home, particularly oxygen concentrators, cost the NHS pounds sterling 18 million, and the number of such prescriptions has been increasing.3 There has never, however, been a completely reliable method for measuring compliance with domiciliary oxygen treatment. The most common method uses a clock incorporated into the oxygen concentrator, but patients may take off their nasal cannulas, and leaving the concentrator and clock running, or they may run the machine without wearing the delivery system. We developed a method to assess compliance that uses plastic electrodes connected …
- Published
- 1994
6. Gregarious Settlement by the Larvae of Hydroides dianthus (Polychaeta: Serpulidae)
- Author
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Scheltema, RS, primary, Williams, IP, additional, Shaw, MA, additional, and Loudon, C, additional
- Published
- 1981
- Full Text
- View/download PDF
7. Significance of Temperature to Larval Survival and Length of Development in Balanus ebumeus (Crustacea: Cirripedia)
- Author
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Scheltema, RS, primary and Williams, IP, additional
- Published
- 1982
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- View/download PDF
8. Tunable control of CAR T cell activity through tetracycline mediated disruption of protein-protein interaction.
- Author
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Hotblack A, Kokalaki EK, Palton MJ, Cheung GW, Williams IP, Manzoor S, Grothier TI, Piapi A, Fiaccadori V, Wawrzyniecka P, Roddy HA, Agliardi G, Roddie C, Onuoha S, Thomas S, Cordoba S, and Pule M
- Subjects
- Animals, Coculture Techniques, Female, HEK293 Cells, Humans, Mice, Protein Binding, Protein Interaction Domains and Motifs, Signal Transduction, T-Lymphocytes immunology, Xenograft Model Antitumor Assays, Minocycline pharmacology, Receptors, Chimeric Antigen metabolism, T-Lymphocytes metabolism
- Abstract
Chimeric antigen receptor (CAR) T cells are a promising form of cancer immunotherapy, although they are often associated with severe toxicities. Here, we present a split-CAR design incorporating separate antigen recognition and intracellular signaling domains. These exploit the binding between the tetracycline repressor protein and a small peptide sequence (TIP) to spontaneously assemble as a functional CAR. Addition of the FDA-approved, small molecule antibiotic minocycline, acts as an "off-switch" by displacing the signaling domain and down-tuning CAR T activity. Here we describe the optimization of this split-CAR approach to generate a CAR in which cytotoxicity, cytokine secretion and proliferation can be inhibited in a dose-dependent and reversible manner. Inhibition is effective during on-going CAR T cell activation and inhibits activation and tumor control in vivo. This work shows how optimization of split-CAR structure affects function and adds a novel design allowing easy CAR inhibition through an FDA-approved small molecule., (© 2021. The Author(s).)
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- 2021
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9. Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma.
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Agliardi G, Liuzzi AR, Hotblack A, De Feo D, Núñez N, Stowe CL, Friebel E, Nannini F, Rindlisbacher L, Roberts TA, Ramasawmy R, Williams IP, Siow BM, Lythgoe MF, Kalber TL, Quezada SA, Pule MA, Tugues S, Straathof K, and Becher B
- Subjects
- Animals, Brain diagnostic imaging, Brain immunology, Brain pathology, Brain Neoplasms diagnostic imaging, Brain Neoplasms immunology, Brain Neoplasms pathology, Cell Line, Tumor transplantation, Disease Models, Animal, ErbB Receptors immunology, Female, Glioblastoma diagnostic imaging, Glioblastoma immunology, Glioblastoma pathology, Humans, Immunoconjugates immunology, Immunoglobulin Fc Fragments administration & dosage, Immunoglobulin Fc Fragments immunology, Injections, Intralesional methods, Interleukin-12 immunology, Magnetic Resonance Imaging, Interventional, Mice, Receptors, Chimeric Antigen immunology, Single-Chain Antibodies administration & dosage, Single-Chain Antibodies immunology, T-Lymphocytes, Regulatory immunology, Tumor Microenvironment immunology, Brain Neoplasms therapy, Glioblastoma therapy, Immunoconjugates administration & dosage, Immunotherapy, Adoptive methods, Interleukin-12 administration & dosage
- Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it is often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor receptor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with a single, locally delivered dose of IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4
+ T cells, decreased numbers of regulatory T cells (Treg), and activation of the myeloid compartment. Importantly, the immunotherapy-enabling benefits of IL-12 are achieved with minimal systemic effects. Our findings thus show that local delivery of IL-12 may be an effective adjuvant for CAR-T cell therapy for GBM.- Published
- 2021
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10. In vivo safety profile of a CSPG4-directed IgE antibody in an immunocompetent rat model.
- Author
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Williams IP, Crescioli S, Sow HS, Bax HJ, Hobbs C, Ilieva KM, French E, Pellizzari G, Cox V, Josephs DH, Spicer JF, Karagiannis SN, and Mele S
- Subjects
- Animals, Antibody-Dependent Cell Cytotoxicity, Antineoplastic Agents, Immunological adverse effects, Cell Line, Tumor, Cross Reactions, Female, Humans, Immunization, Secondary, Immunocompetence, Immunoglobulin E adverse effects, Mice, Rats, Recombinant Fusion Proteins adverse effects, Antigens, Neoplasm immunology, Antineoplastic Agents, Immunological administration & dosage, Chondroitin Sulfate Proteoglycans immunology, Immunoglobulin E administration & dosage, Membrane Proteins immunology, Recombinant Fusion Proteins administration & dosage
- Abstract
IgE monoclonal antibodies hold great potential for cancer therapy. Preclinical in vivo systems, particularly those in which the antibody recognizes the host species target antigen and binds to cognate Fc receptors, are often the closest approximation to human exposure and represent a key challenge for evaluating the safety of antibody-based therapies. We sought to develop an immunocompetent rat system to assess the safety of a rodent anti-tumor IgE, as a surrogate for the human therapeutic candidate. We generated a rat IgE against the human tumor-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) and cross-reactive for the rat antigen. We analyzed CSPG4 distribution in normal rat and human tissues and investigated the in vivo safety of the antibody by monitoring clinical signs and molecular biomarkers after systemic administration to immunocompetent rats. Human and rat CSPG4 expression in normal tissues were comparable. Animals receiving antibody exhibited transient mild to moderate adverse events accompanied by mild elevation of serum tryptase, but not of angiotensin II or cytokines implicated in allergic reactions or cytokine storm. In the long term, repeated antibody administration was well tolerated, with no changes in animal body weight, liver and kidney functions or blood cell counts. This model provides preclinical support for the safety profiling of IgE therapeutic antibodies. Due to the comparable antigen tissue distribution in human and rat, this model may also comprise an appropriate tool for proof-of-concept safety evaluations of different treatment approaches targeting CSPG4.
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- 2020
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11. Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma.
- Author
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Khair DO, Bax HJ, Mele S, Crescioli S, Pellizzari G, Khiabany A, Nakamura M, Harris RJ, French E, Hoffmann RM, Williams IP, Cheung A, Thair B, Beales CT, Touizer E, Signell AW, Tasnova NL, Spicer JF, Josephs DH, Geh JL, MacKenzie Ross A, Healy C, Papa S, Lacy KE, and Karagiannis SN
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal therapeutic use, B7-H1 Antigen immunology, CTLA-4 Antigen immunology, Humans, Immunotherapy methods, Antibodies, Monoclonal immunology, Immune System drug effects, Immune System immunology, Melanoma immunology, Melanoma therapy
- Abstract
The immune system employs several checkpoint pathways to regulate responses, maintain homeostasis and prevent self-reactivity and autoimmunity. Tumor cells can hijack these protective mechanisms to enable immune escape, cancer survival and proliferation. Blocking antibodies, designed to interfere with checkpoint molecules CTLA-4 and PD-1/PD-L1 and counteract these immune suppressive mechanisms, have shown significant success in promoting immune responses against cancer and can result in tumor regression in many patients. While inhibitors to CTLA-4 and the PD-1/PD-L1 axis are well-established for the clinical management of melanoma, many patients do not respond or develop resistance to these interventions. Concerted efforts have focused on combinations of approved therapies aiming to further augment positive outcomes and survival. While CTLA-4 and PD-1 are the most-extensively researched targets, results from pre-clinical studies and clinical trials indicate that novel agents, specific for checkpoints such as A2AR, LAG-3, IDO and others, may further contribute to the improvement of patient outcomes, most likely in combinations with anti-CTLA-4 or anti-PD-1 blockade. This review discusses the rationale for, and results to date of, the development of inhibitory immune checkpoint blockade combination therapies in melanoma. The clinical potential of new pipeline therapeutics, and possible future therapy design and directions that hold promise to significantly improve clinical prognosis compared with monotherapy, are discussed.
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- 2019
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12. Study: is bedside nursing still affected by HIV stigma?
- Author
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Williams IP and Searcy L
- Subjects
- Attitude of Health Personnel, HIV Infections psychology, Humans, HIV Infections nursing, Nursing, Stereotyping
- Published
- 2012
13. Cost-effectiveness analysis and formulary decision making in England: findings from research.
- Author
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Williams IP and Bryan S
- Subjects
- Cost-Benefit Analysis, Drug and Narcotic Control, England, Humans, Interviews as Topic, State Medicine organization & administration, Decision Making, Formularies as Topic, Health Care Rationing economics, Technology Assessment, Biomedical economics
- Abstract
In a context of rapid technological advances in health care and increasing demand for expensive treatments, local formulary committees are key players in the management of scarce resources. However, little is known about the information and processes used when making decisions on the inclusion of new treatments. This paper reports research on the use of economic evaluations in technology coverage decisions in England, although the findings have a relevance to other health care systems with devolved responsibility for resource allocation. It reports a study of four local formulary committees in which both qualitative and quantitative data were collected. Our main research finding is that it is an exception for cost-effectiveness analysis to inform technology coverage decisions. Barriers to use include access and expertise levels, concerns relating to the independence of analyses and problems with implementation of study recommendations. Further barriers derive from the constraints on decision makers, a lack of clarity over functions and aims of local committees, and the challenge of disinvestment in medical technologies. The relative weakness of the research-practice dynamics in this context suggests the need for a rethinking of the role of both analysts and decision makers. Our research supports the view that in order to be useful, analysis needs to better reflect the constraints of the local decision-making environment. We also recommend that local decision-making committees and bodies in the National Health Service more clearly identify the 'problems' which they are charged with solving and how their outputs contribute to broader finance and commissioning functions. This would help to establish the ways in which the routine use of cost-effectiveness analysis might become a reality.
- Published
- 2007
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14. Subsurface radar sounding of the south polar layered deposits of Mars.
- Author
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Plaut JJ, Picardi G, Safaeinili A, Ivanov AB, Milkovich SM, Cicchetti A, Kofman W, Mouginot J, Farrell WM, Phillips RJ, Clifford SM, Frigeri A, Orosei R, Federico C, Williams IP, Gurnett DA, Nielsen E, Hagfors T, Heggy E, Stofan ER, Plettemeier D, Watters TR, Leuschen CJ, and Edenhofer P
- Subjects
- Extraterrestrial Environment, Radar, Spacecraft, Ice, Mars, Water
- Abstract
The ice-rich south polar layered deposits of Mars were probed with the Mars Advanced Radar for Subsurface and Ionospheric Sounding on the Mars Express orbiter. The radar signals penetrate deep into the deposits (more than 3.7 kilometers). For most of the area, a reflection is detected at a time delay that is consistent with an interface between the deposits and the substrate. The reflected power from this interface indicates minimal attenuation of the signal, suggesting a composition of nearly pure water ice. Maps were generated of the topography of the basal interface and the thickness of the layered deposits. A set of buried depressions is seen within 300 kilometers of the pole. The thickness map shows an asymmetric distribution of the deposits and regions of anomalous thickness. The total volume is estimated to be 1.6 x 10(6) cubic kilometers, which is equivalent to a global water layer approximately 11 meters thick.
- Published
- 2007
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15. Managing osteoporosis in older people with fractures. Patients should be given written advice about lifestyle.
- Author
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Yung B, Aram J, Seif A, McManus B, and Williams IP
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- Aged, Female, Humans, Male, Middle Aged, Patient Education as Topic, Fractures, Spontaneous therapy, Life Style, Osteoporosis complications, Steroids administration & dosage
- Published
- 1999
16. Bodybuilders find it easy to obtain insulin to help them in training.
- Author
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Elkin SL, Brady S, and Williams IP
- Subjects
- Humans, Doping in Sports, Insulin supply & distribution, Weight Lifting
- Published
- 1997
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- View/download PDF
17. New method for measuring compliance with long term oxygen treatment.
- Author
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Phillips GD, Harrison NK, Cummin AR, Ward J, Shenoy VS, Newey V, Ritchie D, Williams IP, and Millard FJ
- Subjects
- Electrodes, Home Care Services, Humans, Long-Term Care, Monitoring, Physiologic instrumentation, Reproducibility of Results, Respiratory Insufficiency therapy, Oxygen Inhalation Therapy, Patient Compliance
- Published
- 1994
- Full Text
- View/download PDF
18. Echocardiographic method for the estimation of pulmonary artery pressure in chronic lung disease.
- Author
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Boyd MJ, Williams IP, Turton CW, Brooks N, Leech G, and Millard FJ
- Subjects
- Aged, Blood Pressure Determination methods, Cardiac Catheterization, Chronic Disease, Female, Humans, Hypertension, Pulmonary diagnosis, Hypertension, Pulmonary etiology, Lung Diseases complications, Male, Middle Aged, Echocardiography, Lung Diseases physiopathology, Pulmonary Artery physiopathology
- Abstract
The prognostic implications of pulmonary hypertension in chronic lung disease, and the difficulty in establishing its severity without cardiac catheterisation, indicate the need for a reliable non-invasive method of assessing the pulmonary artery pressure. It is likely that the time taken by the right ventricle to generate a sufficiently high pressure to open the pulmonary valve will increase progressively as the pulmonary arterial diastolic pressure rises. Therefore, the time interval between closure of the tricuspid valve and opening of the pulmonary valve has been obtained by high-speed echocardiographic recordings of the tricuspid and pulmonary valves in a group of 17 patients with chronic lung disease. Each patient underwent right heart catheterisation immediately after the echocardiographic examination so that the pulmonary arterial diastolic pressure could be obtained directly. A range for the group from 15 mmHg (2.0 kPa) to 45 mmHg (6.0 kPa) was observed. The linear correlation between the measured diastolic pressure and time interval from the tricuspid valve closure to pulmonary valve opening was highly significant (r = 0.94, p = less than 0.001) and the scatter was relatively small. It is therefore suggested that this time interval, obtained non-invasively by echocardiography, can be used as an index of the severity of pulmonary hypertension associated with chronic lung disease.
- Published
- 1980
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19. Sympathomimetic drugs stimulate the output of secretory glycoproteins from human bronchi in vitro.
- Author
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Phipps RJ, Williams IP, Richardson PS, Pell J, Pack RJ, and Wright N
- Subjects
- Autoradiography, Bronchi drug effects, Humans, In Vitro Techniques, Moxisylyte pharmacology, Propranolol pharmacology, Secretory Rate drug effects, Stimulation, Chemical, Bronchi metabolism, Glycoproteins metabolism, Sympathomimetics pharmacology
- Abstract
1. We describe a method for supporting pieces of human bronchi in Ussing chambers, for radiolabelling the contents of the secretory cells with 35S, and for collecting radiolabelled macromolecules secreted on to the luminal aspect of the tissue. This method has previously been used to study airway secretions in animals [R. J. Phipps, J. A. Nadel & B. Davis, American Review of Respiratory Disease, (1980) 121, 359-365]. Evidence is given that the radiolabelled molecules are secretory glycoproteins, probably mucus glycoproteins. 2. Phenylephrine, an alpha-adrenoceptor agonist, increased the rate at which the bronchi secreted radiolabelled glycoproteins. Thymoxamine, an alpha-adrenoceptor antagonist, blocked this effect but propranolol, a beta-adrenoceptor antagonist, did not. 3. Dobutamine, a beta-adrenoceptor agonist, increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this but thymoxamine did not. 4. Salbutamol, a beta 2-adrenoceptor agonist, also increased the rate of secretion of radiolabelled glycoproteins. Propranolol blocked this effect. 5. We conclude that both alpha- and beta- adrenoceptor agonists increase the rate of glycoprotein secretion in human bronchi in vitro and that this almost certainly means that they increase the rate of mucus secretion.
- Published
- 1982
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20. Diaphragmatic breathing training and walking performance in chronic airways obstruction.
- Author
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Williams IP, Smith CM, and McGavin CR
- Subjects
- Aged, Female, Humans, Locomotion, Lung Diseases, Obstructive physiopathology, Male, Middle Aged, Respiratory Function Tests, Breathing Exercises, Lung Diseases, Obstructive therapy, Physical Exertion
- Abstract
Eight patients with chronic obstructive bronchitis and moderate disability entered a pilot study of the effects of controlled diaphragmatic breathing. They received three weeks of placebo physiotherapy (shoulder exercises) followed by three weeks of instruction on controlled diaphragmatic breathing. No beneficial effects were observed on exercise performance or the perceived strain of exercise.
- Published
- 1982
21. Can patients keep their own peak-flow records reliably?
- Author
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Hetzel MR, Williams IP, and Shakespeare RM
- Subjects
- Adolescent, Adult, Aged, Asthma physiopathology, Bronchitis physiopathology, Cardiovascular Diseases physiopathology, Child, Evaluation Studies as Topic, Female, Humans, Male, Middle Aged, Rheology, Forced Expiratory Flow Rates instrumentation, Hospital Records, Lung physiopathology, Monitoring, Physiologic instrumentation, Patients, Peak Expiratory Flow Rate instrumentation, Records, Respiratory Tract Diseases physiopathology
- Abstract
Fifty patients recorded their peak expiratory-flow rate (P.E.F.R.) in hospital, unaided by nursing staff, five times a day for 5 days. Each patient's readings were randomly and independently checked on two occasions during this period. 69% of checked readings were accurate. Most patients kept satisfactory records as a table, but were less efficient in recording their results on a P.E.F.R. chart. Recording of P.E.F.R. by patients with respiratory disease saves nursing time and provides valuable clinical information.
- Published
- 1979
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22. Severe asthma after inadvertent ingestion of oxprenolol.
- Author
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Williams IP and Millard FJ
- Subjects
- Adult, Bronchial Spasm chemically induced, Female, Humans, Asthma chemically induced, Oxprenolol poisoning
- Published
- 1980
- Full Text
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23. Tuberculous pericarditis in South-west London: an increasing problem.
- Author
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Williams IP and Hetzel MR
- Subjects
- Adult, Africa, Eastern ethnology, Asia ethnology, Female, Humans, London, Male, Middle Aged, Pericarditis, Tuberculous drug therapy, Prednisone therapeutic use, Pericarditis, Tuberculous epidemiology, Tuberculosis, Cardiovascular epidemiology
- Published
- 1978
- Full Text
- View/download PDF
24. Corticosteroids in chronic airways obstruction: can the patient's assessment be ignored?
- Author
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Williams IP and McGavin CR
- Subjects
- Airway Obstruction physiopathology, Chronic Disease, Female, Forced Expiratory Volume, Humans, Male, Vital Capacity, Airway Obstruction drug therapy, Outcome and Process Assessment, Health Care, Patient Participation, Prednisolone therapeutic use
- Abstract
In a study to examine the methods of assessing the response of patients with chronic airways obstruction to corticosteroids, 20 patients received a week of placebo tablets, followed by three weeks of prednisolone 30 mg daily. Subjective benefit was assessed by a visual analogue scale (VAS), and objective changes by spirometry and an exercise test. Significant increases in FEV1 and in exercise performance were observed after steroid therapy. Changes in FVC correlated both with VAS score and with changes in exercise performance. Changes in FEV1 correlated with neither. The good correlation between the changes in a ventilatory function test (the FVC) and the patients' assessments of the drug suggests that the non-specific euphoriant effect of steroids does not eclipse their specific action on ventilatory function. Assessment of benefit should include a subjective assessment and changes in FVC and exercise performance. Changes in FEV1 appear to have less clinical relevance.
- Published
- 1980
- Full Text
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25. Action of serum on the output of secretory glycoproteins from human bronchi in vitro.
- Author
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Williams IP, Rich B, and Richardson PS
- Subjects
- Humans, In Vitro Techniques, Secretory Rate, Blood Physiological Phenomena, Bronchi metabolism, Mucins metabolism
- Abstract
The effect on mucin output of placing dilute serum from healthy donors in contact with the luminal surface of human airway has been studied. Bronchi were dissected from lungs removed at operation. Mucins, radiolabelled biosynthetically, were collected from the luminal aspect of the bronchi, which were mounted in Ussing chambers. Serum added to the luminal aspect of the tissue, at dilutions ranging from 1:100 to 1:10 of Krebs-Henseleit solution, consistently increased the output of radiolabelled mucins. The concentrations of serum tested in these experiments lie within the range commonly found in sputum coughed from the lungs of those with inflamed airways. Serum diluted to 1:2500, which is roughly the concentration found in the normal human airway, had little or no effect on bronchial secretion. Increased leakage of serum into the inflamed airways is suggested as one of the stimuli that increase bronchial secretion.
- Published
- 1983
- Full Text
- View/download PDF
26. Effects of prostaglandins E1, E2, and F2 alpha on mucin secretion from human bronchi in vitro.
- Author
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Rich B, Peatfield AC, Williams IP, and Richardson PS
- Subjects
- Alprostadil, Bronchi drug effects, Dinoprost, Dinoprostone, Humans, In Vitro Techniques, Secretory Rate drug effects, Bronchi metabolism, Mucins metabolism, Prostaglandins E pharmacology, Prostaglandins F pharmacology
- Abstract
The effects of three prostaglandins on the output of 35S labelled mucus glycoproteins (mucins), from explants of human bronchial tissue suspended in Ussing chambers, have been investigated. Prostaglandin F2 alpha, added to the Krebs-Henseleit solution bathing both luminal and submucosal sides of the tissue, significantly increased mucin output at concentrations of 0.1 and 1.0 micrograms/ml (0.28 and 2.8 microM), 11 preparations being used for each dose. Since prostaglandin F2 alpha has been shown to be released from human airways challenged by antigen, it may be important in the regulation of mucus secretion in these circumstances. Prostaglandins E1 and E2 had no significant effects on mucin output even at the highest concentration (1.0 micrograms/ml), though in half the tissues tested PGE2 stimulated secretion consistently. These results contrast with the findings in a previous study, which showed an inhibition of mucin output by PGE2.
- Published
- 1984
- Full Text
- View/download PDF
27. A preparation for the study of secretory function of the human bronchus in vitro.
- Author
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Pack RJ, Williams IP, Phipps RJ, Richardson PS, and Rich B
- Subjects
- Autoradiography, Bronchi anatomy & histology, Culture Techniques, Cytoplasmic Granules ultrastructure, Epithelium anatomy & histology, Exocrine Glands anatomy & histology, Exocrine Glands metabolism, Glycoproteins metabolism, Humans, Microscopy, Electron, Scanning, Bronchi metabolism, Mucus metabolism
- Abstract
Bronchi, not involved in tumor, were removed from resected human lungs. They were mounted in Ussing chambers containing Krebs-Henseleit solution with radiolabelled precursors of mucus. Airway was examined by both light and electron microscopy. Tissues recently removed from resected lungs exhibited both intra- and extra-cellular oedema and hypoxic changes in mitochondria, but tight junctions between epithelial cells appeared intact, indicating an effective epithelial barrier. Tissues removed from Ussing chambers after up to 6 h showed little oedema and their mitochondria were normal. Their appearance had returned to that of specimens taken that biopsy and fixed immediately. Autoradiographs of specimens from Ussing chambers showed that the mucus-producing cells had concentrated the radiolabels . Mucus in gland ducts was also radiolabelled. Damaged areas of mucous membrane were rare and probably pre-operative. We conclude that resected bronchi, suspended in Ussing chambers, have a structure and secretory activity suitable for investigations of the control of secretion.
- Published
- 1984
28. The effects of oral propranolol and metoprolol on lung function and exercise performance in chronic airways obstruction.
- Author
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McGavin CR and Williams IP
- Subjects
- Administration, Oral, Aged, Airway Obstruction physiopathology, Chronic Disease, Clinical Trials as Topic, Double-Blind Method, Humans, Male, Metoprolol administration & dosage, Middle Aged, Physical Exertion, Propranolol administration & dosage, Random Allocation, Respiratory Function Tests, Airway Obstruction drug therapy, Metoprolol therapeutic use, Propanolamines therapeutic use, Propranolol therapeutic use
- Abstract
Fifteen men with chronic airways obstruction received a test dose of propranol 20 mg orally. Six developed increased breathlessness. Nine who tolerated the test dose received metoprolol (100 mg) and propranolol (80 mg) on different days in a randomized double-blind fashion. Changes in resting and exercise heart rate, spirometry and exercise tolerance were measured 1 and 6 hours later. The drugs had similar effects on heart rate. Propranolol, but not metoprolol, caused significant reduction in forced expiratory volume in one second (FEV1) and peak expiratory flow rate. Neither drug produced significant changes in forced vital capacity (FVC) or exercise performances in the group as a whole, although the range of changes was wide. Despite considerable reduction in FEV1 and FVC in some individuals, most reported no increase in symptoms. Changes in exercise tolerance at 1 hour correlated significantly with changes in FVC but not with those in FEV1. It is proposed that changes in FEV1, though of pharmacological interest, may be less relevant clinically than changes in FVC.
- Published
- 1978
29. Laser treatment for carcinoma of the bronchus.
- Author
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Hetzel MR, Millard FJ, Ayesh R, Bridges CE, Nanson EM, Swain CP, and Williams IP
- Subjects
- Aged, Bronchial Neoplasms complications, Bronchial Neoplasms mortality, Carcinoma, Squamous Cell complications, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell surgery, Female, Hemoptysis etiology, Humans, Lasers adverse effects, Lung Diseases, Obstructive etiology, Male, Middle Aged, Bronchial Neoplasms surgery, Laser Therapy
- Abstract
Laser treatment in carcinoma of the bronchus is essentially palliative and is suitable for only a few patients. Patients selected for laser treatment must have predominantly endobronchial growth with normal bronchial anatomy still identifiable and symptoms due to the obstruction or to haemoptysis. A total of 34 patients with carcinoma of the bronchus were treated with argon gas or neodynium yttrium aluminium garnet crystal lasers. Good palliation was obtained in just over half the cases of partial obstruction of the trachea or main bronchus, but best results were obtained in lesions of the trachea or main carina. Re-expansion of the collapsed lung was achieved in some cases but with considerable risk of pneumonia. Haemoptysis was controlled at least partly in several cases. Laser treatment has the advantage of having no toxicity or dose limit and may be used in cases of poor respiratory function. The procedure was better tolerated than radiotherapy or chemotherapy and its relatively lower cost may justify setting up laser units in major cities.
- Published
- 1983
- Full Text
- View/download PDF
30. Pulmonary arterial hypertension and emphysema.
- Author
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Williams IP, Boyd MJ, Humberstone AM, Wilson AG, and Millard FJ
- Subjects
- Aged, Blood Pressure, Female, Humans, Male, Middle Aged, Oxygen blood, Partial Pressure, Pulmonary Emphysema physiopathology, Respiratory Function Tests, Hypertension, Pulmonary etiology, Pulmonary Emphysema complications
- Abstract
Pulmonary artery pressures were estimated by an indirect method using echocardiography (Boyd et al. 1980), in a group of patients with chronic airflow obstruction, in order to investigate the degree of pulmonary hypertension in patients with emphysema. We found a positive correlation between the estimated pulmonary artery end diastolic pressure (PAEDP) and the radiological emphysema score (r = 0.58, P less than 0.005), and between the estimated PAEDP and the transfer constant for carbon monoxide (KCO) (r = 0.66, P less than 0.002). There was no correlation between the PAEDP and the arterial partial pressure of oxygen (PaO2) before exercise, between the PAEDP and the change in oxygen partial pressure after exercise, or between the KCO and the PaO2. It is suggested that emphysema does predispose to pulmonary arterial hypertension and that the relationship is probably secondary to vessel destruction rather than hypoxia.
- Published
- 1984
31. Cutaneous tuberculosis in an asian.
- Author
-
Hetzel MR and Williams IP
- Subjects
- Adult, Asia ethnology, Humans, Kenya ethnology, Male, United Kingdom, Tuberculosis, Cutaneous diagnosis
- Published
- 1979
32. Analyses of human tracheobronchial mucus from healthy subjects.
- Author
-
Williams IP, Hall RL, Miller RJ, and Richardson PS
- Subjects
- Adult, Alcian Blue, Blood Chemical Analysis, Bronchi metabolism, Chemical Fractionation, Dithioerythritol, Female, Humans, Male, Middle Aged, Spectrophotometry, Trachea metabolism, Mucus analysis
- Abstract
Tracheobronchial mucus was obtained from four healthy subjects by fibreoptic bronchoscopy. The material was fractionated by gel exclusion chromatography on a Sepharose CL2B column. One peak of optical density 280 nm was found in the excluded volume and another in the included volume suggesting that these contained the majority of the aromatic amino acids. Alcian Blue was used to precipitate acidic glycoproteins in each fraction. When the dye had been redissolved two peaks of optical density at 620 nm were detected, in the excluded and included volumes respectively, and these peaks corresponded with the absorbance at 280 nm. The elution profiles were similar to those given by mucins from other systems. Treatment with urea and dithiothreitol caused no change in the elution profile so there is no evidence that disulphide bonds link glycoprotein subunits in airway mucus from healthy subjects.
- Published
- 1982
33. The sympatomatic treatment of carcinoma of the bronchus using combination chemotherapy.
- Author
-
Williams IP, Clein GP, Ford HT, and Millard FJ
- Subjects
- Adult, Aged, Bronchial Neoplasms mortality, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Drug Therapy, Combination, Female, Humans, Leucovorin therapeutic use, Male, Methotrexate therapeutic use, Middle Aged, Prednisolone therapeutic use, Vincristine therapeutic use, Antineoplastic Agents administration & dosage, Bronchial Neoplasms drug therapy
- Abstract
A study was made of chemotherapy for inoperable carcinoma of the bronchus. Only patients with symptoms directly due to the tumour or with evidence of rapid tumour growth were selected for treatment. Half the patients selected in this way responded and in these patients survival may have been prolonged. The regimen chosen caused the minimum of interference with the patient's life and, by relief of symptoms, appeared to offer an improvement in the quality of life.
- Published
- 1978
- Full Text
- View/download PDF
34. Detection and reversal of pulmonary absorption collapse.
- Author
-
Nunn JF, Williams IP, Jones JG, Hewlett AM, Hulands GH, and Minty BD
- Subjects
- Adult, Carbon Dioxide blood, Functional Residual Capacity, Humans, Male, Middle Aged, Oxygen blood, Pulmonary Atelectasis diagnostic imaging, Pulmonary Atelectasis physiopathology, Radiography, Pulmonary Atelectasis diagnosis
- Published
- 1978
- Full Text
- View/download PDF
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